Regulation of interleukin-13 by type 4 cyclic nucleotide phosphodiesterase (PDE) inhibitors in allergen-specific human T lymphocyte clones

David M. Essayan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein, Shau Ku Huang

Research output: Contribution to journalArticle

Abstract

Interleukin-13 (IL-13) is a proinflammatory cytokine of T cell origin. Structural and functional studies suggest a key role for IL-13 in the genesis of chronic allergic inflammation; as such, its pharmacologic inhibition is of potential clinical utility. We studied the pharmacologic regulation of IL- 13 expression by cyclic nucleotide phosphodiesterase (PDE) inhibitors in a panel of Amb a 1 (a major allergen of short ragweed, Ambrosia artemisiifolia)- specific T cell clones derived from a ragweed allergic, asthmatic subject. Proliferative responses of these cells were down-regulated by rolipram, a PDE4 inhibitor (% inhibition(MAX) = 67%; IC50 = 20 μM). While the PDE3 inhibitor siguazodan provided no independent efficacy (IC50 > 10-4 M), an increased efficacy of rolipram m the presence of 10-5 M siguazodan was noted at 10-6, 10-5, and 10-4 M rolipram (P < 0.03, 0.01, and 0.04, respectively). The EC50 values remained unchanged between assays using the PDE4 inhibitor with or without the PDE3 inhibitor. Both IL-13 gene expression and protein secretion into culture supernatants were down-regulated by the PDE4 inhibitor (P ≤ 0.005). Once again, the use of a PDE3 inhibitor provided no independent efficacy (P ≤ 0.2), and in this instance, increased efficacy of the PDE4 inhibitor with the PDE3 inhibitor was not apparent (P ≤ 0.3). IL-13 production from clones with Th0, Th1, and Th2 phenotypes appeared equally sensitive to treatment with the PDE4 inhibitor. We conclude that the anti-inflammatory effects of PDE4 inhibitors may be mediated, in part, by down-regulation of IL-13.

Original languageEnglish (US)
Pages (from-to)1055-1060
Number of pages6
JournalBiochemical Pharmacology
Volume53
Issue number7
DOIs
StatePublished - Apr 4 1997

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Keywords

  • T lymphocyte
  • allergy
  • cAMP
  • human
  • interleukin-13
  • phosphodiesterase

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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